The WHO International Task Force for Disease Eradication had identified
lymphatic filariasis (LF) as one of only six potentially eradicable diseasesin the year 1993 (CDC, 1993). Based on
this the World Health Assembly resolvedin the year 1997, to eliminate lymphatic
filariasis as a public health problem globally (Ottesen, 1998). In accordance to
this and consequent on several recent advances in the diagnosis and treatment of
LF, the World Health Organization launched the Global Programme for Elimination
of LF (GPELF) with an aim to eliminate this disease globally by 2020. India, a
signatory to the World Health Assembly resolution, has set the target for
elimination of filariasis by the year 2015. This programme is based on a dual
approach consisting of (i) interruption of transmission to prevent the disease
by mass drug administration (MDA) and (ii) alleviation of the disability in
those who already have the disease (Seim et al., 1999).

To
support GPELF by raising funds and helping in various other ways, a global
coalition was forged among 43 different donors constituting the Global Alliance
to Eliminate Lymphatic Filariasis (GAELF). One of the partners GlaxoSmithKline
has volunteered to supply the total quantity of albendazole tablets required to
eliminate LF globally, free of cost (WHO, 2002). They have thus supplied more
than 200 million tablets by now. The Diethylcarbamazine (DEC) tablets needed for
the programme in India is being supplied by the Central Government.

LYMPHATIC FILARIASIS:

Lymphatic filariasis (LF) is a parasitic disease caused by thin, thread-like
filarial worms transmitted to humans by the bite of mosquitoes. The adult worms
lie deep in the lymph vessels of the scrotum, groin, armpit and around the
breasts where they may live for 4-6 years. These worms grow and mature in the
lymph vessels and produce millions of baby worms called microfilaria (mf), which
appear in the peripheral blood at night and can be identified to certain extent
by night blood examination. When the mosquito bites a person having microfilaria
in his blood, it takes in microfilaria also along with the blood. In the
mosquito microfilaria develop into infective larvae in 7 - 21 days. When this
mosquito bites another person, he gets infected.

The two parasite species prevalent in India causing LF are
the nocturnally periodic forms of Wuchereria bancrofti transmitted by Culex
quinquefasciatus and Brugia malayi transmitted by Mansonia mosquitoes. The
former is responsible for nearly 95% of the national disease burden and the
latter accounts for the remaining.

The adult filarial worms living in the lymphatics are responsible for the
initial changes in these vessels, which predispose to the later development of
clinical manifestations. Filariasis is the commonest cause of lymphoedema and
hydrocele in India. Attacks of acute adenolymphangitis (ADL) associated with
fever and painful swelling of the affected limbs commonly occur in these
patients.

Incidence of LF:

An estimated total of 120 million people are infected
globally with LF, which is ranked as the second most common cause of physical
disability. Among the debilitating vector-borne tropical diseases LF isnext only to malaria (WHO, 1995).
India alone contributes to about 40% of the global filariasis disease burden and
harbors 50% of the global population at risk of infection (Michael et al.,
1996). While W. bancrofti infection is endemic in 17 States and 6 Union
territories, B. malayi is limited to some areas in Kerala and in 7 other States
(WHO, 1992; NFCP, 1995). A recent mapping of the district level endemicity of LF
has shown that out of the 289 districts surveyed, 257 are endemic for this
disease (Sabesan et al., 2000). India has a total of 31.26 million
microfilaraemics; 7.44 million having lymphoedema and 12.88 million suffering
from hydrocele and it is estimated that in this population, a total of 40.65
million episodes of acute adenolymphangitis (ADL) occur in a year. The total
disability adjusted life years (DALYs) lost in India due to this disease are
around 2.06 million, resulting in an annual wage loss of US $ 811 million (Ramaiah
et al., 2000).

LF - A childhood
disease:

Contrary to earlier belief, several recent studies have indicated that LF is
first acquired during childhood, even though the clinical disease manifests only
later in adult life. In endemic areas the blood microfilaria (mf) prevalence
rates in children were found to be ~30% of adult prevalence for <10 year olds
and ~ 69% for 10-19 years olds (Witt & Ottesen, 2001). The ICT card test showed
filarial antigenaemia in 6% of the two-year old children, which increased to 30%
in four-year olds(Lamie et al.,
1998). In a study from Madurai it is reported that 92.3% of children in the age group of 2-5 years
were circulating filaria antigen (CFA) positive, when their blood smear was
negative for mf. The antigenaemia was highest among the 5 years old children (Sunish
et al., 2001).

Ultrasonography and lymphoscintigraphy have helped to understand the early
changes in the lymphatics brought about by the adult worms. Abnormalities of the
lymph vessels like dilation of lymph vessels and renal involvement in the form
of microscopic haematuria have been demonstrated even in early stages of the
infection, when the affected person had only microfilaria in the blood without
any overt clinical disease (Dreyer et al., 1992; 1999). The important fact is
that once established, this early lymphatic pathology appears to be irreversible
even with treatment, causing progression of the disease (Freedman et al., 1995).

One interesting aspect of LF is that in the early stages of the disease when the
person harbors the adult worms in the lymph vessels and has microfilaria in the
blood there is no outward evidence of any disease. By the time the person
develops swelling of the limbs, usually there are no microfilaria in the blood
and CFA tends to be negative, especially in established cases of lymphoedema.
But hydrocele may be associated with antigenaemia and microfilaraemia.

Sufferings caused by
the disease:

Many recent studies have illustrated the devastating social, psychological,
sexual and economic issues due to the deformities caused by this disease. The
massive swellings of the limbs in elephantiasis interfere with the day to day
activities of these patients. Genito-urinary disease, especially hydrocele,
results in strong feelings of shame, fear and embarrassment associated with
sexual disability and dysfunction. It is the repeated attacks of ADL more than
the swelling of the limbs that incapacitate the patients with LF, calling for
urgent medical intervention.

Inability to care for self, isolation from the community, loss of social support
and family stress are the other problems faced by these patients. This disease
hampers the marriage prospects of the young, mainly females. Other social
problems among young patients include feeling of shame, embarrassment and
frequent absence from or even discontinuation of studies.

In
the light of this knowledge, it is important that steps are initiated to prevent
this disease in the population at risk, so that the next generation is free of
this horrid malady.

MASS DRUG
ADMINISTRATION:

Recent studies have shown that annual administration of single dose of
antifilarial drugs keep down the microfilaria levels in the blood to very low
levels even at the end of the year. It is shown that the drug has to be given
once every year for 4-6 years, which is the duration of the reproductive phase
in the life cycle of the filarial worms (Ottesen et al., 1997).

The spread of the disease depends on the load of microfilaria in the blood of
individuals in a community and the presence of appropriate mosquito species.
Bringing down the levels of microfilaria in blood will prevent spread of this
disease since mosquitoes will then fail to pick them up and transmit the
disease. To effectively prevent the transmission of filariasis by the mosquito,
the drugs have to be consumed every year by at least by 80% of the eligible
population in the endemic States.

Why all persons
should take the drugs:

So far the diagnosis of LF infection depended on the demonstration of the
microfilaria in the peripheral blood obtained by finger prick at night. There
are several fallacies in the blood examination. The mf appear in peripheral
blood between 10pm and 2am. Most often
the blood examination is done before this time. The preparation, staining of the
blood smear, effort put in identifying the parasite etc. are important factors
in detecting infection. These are often not carried out satisfactorily and many
LF infections are missed. In early stages of infection, especially in children
mf may be absent from blood since the adult worms have not started producing mf
or when only adult parasites of single sex are present.

Results of recent filaria antigen detection methods using ICT card and Og4C3
ELISA have shown that night blood examination is not sensitive enough to detect
all parsons who are infected (Weil et al., 1996). Several studies have shown
that the percentage of prevalence of LF as indicated by antigen detection
methods is always much higher than the mf detection through night blood
examination (Lammie et al., 1994). In a report from Tamil Nadu, India the
prevalence of antigenaemia was found to be 11.3 - 12.7% more than microfilaria
prevalence rates in all age groups (Sunish et al., 2002).

The above findings stress the importance of treating all persons 'at risk' of
infection in a community by MDA, because all infected people cannot be
identified presently by night blood examination. The antigen detection methods
are costly and are not available to screen whole populations.

Vector control:
In the past various methods were used for mosquito control, including integrated
approach together with identification of LF infection in individuals and
treatment. Over the years, in most of the endemic countries these methods have
failed to control LF and they were not cost effective. Vector control will be a
useful adjunct to MDA if it is practiced at the community level through
participation of people and at a lesser cost.

DRUGS USED IN MDA:

Diethylcarbamazine (DEC):
This drug, which is being used in the control and treatment of LF during the
last 57 years, has stood the test of time. This is the drug of choice for both
W.bancrofti and B.malayi infections.DEC is very effective in destroying
microfilaria in the blood and hence is a very effective tool in prevention of
transmission of infection. Its action against the adult worms is variable as has
been made out by ultrasound examination, which has shown that the adult
parasites are killed in only ~50% of persons harboring them. Ultrasonography has
also shown that single dose of DEC kills the adult worms when they are sensitive
to this drug. If they are insensitive, even repeated doses do not have any
effect (Noroes et al., 1997). For the past several years the recommended dose of
DEC in LF was 6 mg/kg daily for 12 days (WHO, 1992). However recent drug trials
have shown that a single dose of 6 mg/kg is as effective as the 12 days course (Ottesen
et al., 1997). Single annual administration of 6 mg/kg DEC results in sustained
lowering of blood microfilaria levels even at the end of one year(Shenoy et al., 1993; Andrade et al.,
1995; Ottesen, 2000).

Due to its sustained microfilaricidal action even in single annual doses, DEC is
a good tool to prevent the transmission of LF (Ottesen et al., 1997; Ottesen,
2000a). The adverse effects noticed with DEC are mostly in subjects who have
microfilaraemia due to their rapid destruction. Characterized by fever,
headache, myalgia, sore throat or cough that last from 24 to 48 hours, these
symptoms are usually mild, self-limiting and require only symptomatic treatment
(Andrade et al., 1995; Addiss et al., 2000). Direct adverse effects related to
the drug are very rare. Studies have shown that the side effects are well
correlated with the level of microfilariae.

Even though DEC is conventionally not recommended for administration during
pregnancy, in several earlier community studies where this drug was used for
mass distribution, no adverse effect has been reported in pregnant women (Ottesen
et al., 1997). This drug is reported to be safe for use in pregnancy (Hardman et
al., 1996; Moore, 2001)

Albendazole:
This well-known anthelmintic drug when given in annual single dose of 400 mg in
combination with DEC or ivermectin there is sustained lowering of blood
microfilaria levels (Shenoy et al., 2000). Consequent on this effect and its
action against many intestinal parasites, albendazole combined either with DEC
or ivermectin is recommended for the filariasis elimination programme (Ottesen
et al., 1997).

PRESENT SCENARIO OF
GELF:

The Global Programme for Elimination of Filariasis is presently being carried
out in 38 out of the 83 endemic countries in the world using DEC and Albendazole.
In countries like Solomon Islands, Costa Rica, Surinam, Trinidad, Tobago and
Egypt, the prevention of transmission of the disease has become a reality.

In
the year 2000, 2.9 million people in 12 countries were covered by MDA and in
2001, this was increased to 28.89 million. In 2002, 60 million people in 34
countries were covered and in 2003 it was 100 million people in 38 countries. In
the year 2004 - 2005, in India 202 endemic districts having a population of 408
million were brought under MDA (NVBDCP, 2005). So far no serious adverse
reactions to DEC or DEC + albendazole are reported in the MDA, other than the
mild to moderate symptoms due to the large scale killing of mf in the blood.
This strategy recommended by the World Health Organization has proved to be safe
for the treated communities (Molyneux, 2003).

It
is seen that in India, the actual number of people who consumed the drug during
MDA is far less than the 80% coverage required to prevent transmission of
filariasis. Studies have shown that if higher coverage is not achieved, the drug
administration will have to be continued for many more years.

CONCLUSION:

At
present the only available and effective method to eliminate LF is the properly
conducted MDA. Now that the whole world is pursuing the goal of elimination of
lymphatic filariasis, this is the right time to put all our effort for the
success of this national programme because of the high prevalence of this
disease in India.